Artificial particulate systems such as polymeric beads and liposomes are finding a variety of biomedical applications in drug delivery, drug targeting, protein separation, enzyme immobilization and blood cell substitution. Liposomes have a flexible, cell-like lipid bilayer surface which acts as a permeability barrier such that compounds can be entrapped in their aqueous interior. However, liposomes can be mechanically unstable and their loading capacity limited by the water solubility of the material to be loaded. Other approaches for the preparation of nanometer- to micrometer-sized spherical polymer shells involve the layer-by-layer deposition of polyelectrolytes on the surface of a charged nanoparticle followed by the dissolution of the templating particle or the self assembly of amphiphilic diblock copolymers into micelles, selective cross-linking of their hydrophilic shell, and subsequent degradation of the hydrophobic core. Preparation of such nanocapsules requires a rather complex process. Also, polymeric beads, although mechanically more stable and having a larger loading capacity than liposomes, lack many of the useful surface properties of a lipid bilayer shell.
Drug targeting systems have been described in various patent publications and scientific articles. Specific antibodies carrying diagnostic or therapeutic agents targeted to the site of action displaying the corresponding antigen are widely used (Vyas S. P. et al., Crit Rev Ther Carrier Syst 2001, 18(1):1-76).
Nanoparticles have been studied extensively as particulate carriers in several pharmaceutical and medical fields (Sakuma S. et al., Adv Drug Del Rev 2001, 47:21-37). It is well known that the bioavailability of peptide and protein drugs after oral administration is very low because of their instability in the gastrointestinal (GI) tract and low permeability through the intestinal mucosa. Therefore, injectable dosage forms are currently used to obtain therapeutic effects. However, since these administration routes are poorly accepted by patients, it is indispensable to develop alternatives such as nasal, buccal, rectal, vaginal, pulmonary and transdermal routes. Oral administration is the most convenient route for drug delivery, and several approaches such as chemical modification to alter the physicochemical properties of peptide drugs, the use of an absorption enhancer to promote drug absorption and the use of a protease inhibitor to protect drugs against degradation by enzymes have been investigated in Order to achieve oral peptide delivery. Nanoparticles have been studied as carriers for oral drug delivery. The aims of the studies done on nanoparticles as oral drug carriers were improvement of the bioavailability of drugs with poor absorption characteristics, delivery of vaccine antigens to the gut-associated lymphoid tissues, control of the release of drugs, reduction of the GI mucosa irritation caused by drugs, and assurance of the stability of drugs in the GI tract.
Also circulation times in the blood can be modified by particulate administration of drugs. The need for recirculation of therapeutic agents in the body, that is avoidance of rapid endocytosis by the reticuloendothelial system and avoidance of rapid filtration by the kidney, to provide sufficient concentration at a targeted site to afford necessary therapeutic effect has been recognized. Small molecules, such as gadolinium diethylenetriaminepentaacetic acid, tend to have limited circulation times due to rapid renal excretion while most liposomes, having diameters greater than 800 nm, are quickly cleared by the reticuloendothelial system.
The traditional immunization arsenal includes vaccines that use live attenuated organisms, inactivated organisms, conventional whole proteins, and, more recently, naked DNA. From an immunological standpoint, based on the broad range of humoural and cellular immune responses generated and the memory responses they induce, live attenuated vaccines still represent the vaccines of choice (BenMohammed L. et al., Lancet Infect Dis 2002, 2:425-431). From a practical and safety standpoint, however, live attenuated vaccines raise issues related to manufacturing and safety that may preclude their widespread use. As an alternative, peptide-based vaccines have now been developed and used for vaccination. Peptide-based vaccines offer several potential advantages over the conventional whole proteins (or whole gene, in the case of genetic immunization) in terms of purity and a high specificity in eliciting immune responses. However, synthetic peptides alone are often not immunogenic enough, and a strong immunoadjuvant is usually employed for their elaboration. Concerns about toxic adjuvants, however, which are critical for immunogenicity of synthetic peptides, still remain. And maybe even more critical is the problem of human genetic heterogeneity, which results in varying strength of immune responses.
One potential solution for stabilizing peptide-based vaccines is the presentation of epitopes embedded in a coiled-coil peptide composition as described in WO 01/00010. Viral particles, in particular particles formed from hepatitis virus B surface antigens, have been considered as nanoparticles useful for antigen presentation (EP 201 416) or for the transport of substances into target cells and tissue (EP 1262 555).
There is a need for improved types of mechanically and chemically stable vesicles and nanocapsules to be used for drug targeting and antigen presentation.